This application requests five years of salary support for Dr. Diane Lipscombe to develop her research program that addresses the regulation and function of neuronal calcium channels. The three main projects proposed incorporate modern molecular and electrophysiological methods to study Ca2+ channel structure, regulation, expression and function in both normal and neuropathological states. The first project addresses the structure and regulation of an N-type calcium channel cloned from sympathetic neurons. The second, an assessment of the functional importance in sympathetic neurons, of the expression of different potential splice variants of the N type Ca2+ channel; and in the third, in a collaborative study with Dr. Heidi Scrable (Univ. Virginia), the potential role of Ca2+ channels in the pathophysiology of Type l neurofibromatosis. Brown University provides an exceptionally strong environment to develop this research program and is fully supportive of Dr. Lipscombe's career plans. Brown University already has highly respected Neuroscience research programs as well as training at the graduate and undergraduate level. In recognition of the Department's accomplishments the University has committed substantial new resources towards further development of the neurosciences at Brown. The Department, including Dr. Lipscombe's laboratories, will be newly renovated and expanded by May 1996, with a major new commitment to cell and molecular neurobiology. The expansion will include new tissue culture and molecular facilities and four new tenure-track faculty positions; two in molecular neurobiology and two in the area of synaptic function and learning and memory. During the award period Dr. Lipscombe will further develop her research skills through substantial additional time made available for (1) independent and collaborative work in her laboratory, (2) additional coursework in molecular neurobiology and, (3) increased interactions with members of the Brown Departments of Neuroscience and Molecular and Cell Biology and Biochemistry. This award is requested at a critical time for Dr. Lipscombe to devote herself fully to projects which are already providing new and important insights into Ca2+ channel function. The proposed plan is fully endorsed by Brown University.